Details

Autor(en) / Beteiligte

• Kleinpeter, Erich
• Taddei, Ferdinando
• Wacker, Philipp

Titel

Electronic and Steric Substituent Influences on the Conformational Equilibria of Cyclohexyl Esters: The Anomeric Effect Is Not Anomalous

Ist Teil von

• Chemistry : a European journal, 2003-03, Vol.9 (6), p.1360-1368

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2003

Quelle

Wiley Online Library

Beschreibungen/Notizen

• The cyclohexyl esters of a series of carboxylic acids, RCO2H, spanning a range of electronegativities and quotients of steric hindrance for the R substituent (R=Me, Et, iPr, tBu, CF3, CH2Cl, CHCl2, CCl3, CH2Br, CHBr2, and CBr3) were prepared. Their conformational equilibria in CD2Cl2 were examined by low‐temperature 1H NMR spectroscopy to study the axial or equatorial orientation of the ester functionality with respect to the adopted chair conformation of the cyclohexane ring. The ab initio and DFT geometry‐optimized structures and relative free energies of the axial and equatorial conformers were also calculated at the HF/6‐311G**, MP2/6‐311G**, and B3LYP/6‐31G** levels of theory, both in the gas phase and in solution. In the latter case, a self‐consistent isodensity polarized continuum model was employed. Only by including electron correlation in the modeling calculations for the solvated molecules was it possible to obtain a reasonable correlation between ΔG°calcd and ΔG°exp. Both the structures and the free energy differences of the axial and equatorial conformers were evaluated with respect to the factors normally influencing conformational preference, namely, 1,3‐diaxial steric interactions in the axial conformer and hyperconjugation. It was assessed that hyperconjugative interactions, σCC/σCH and σ*CO, together with a steric effect—the destabilization of the equatorial conformer with increasing bulk of the R group—were the determinant factors for the position of the conformational equilibria. Thus, because hyperconjugation is held responsible as the mitigating factor for the anomeric effect in 2‐substituted, six‐membered saturated heterocyclic rings, and since it is also similarly responsible, at least partly, in these monosubstituted cyclohexanes for a preferential shift towards the axial conformer, the question is therefore raised: can the anomeric effect really be construed as anomalous? Hyperconjugative interactions, σCC/σCH and σ*CO, together with a steric effect—the destabilization of the equatorial conformer with increasing bulk of the R group—are the determinant factors for the position of the conformational equilibria of mono‐substituted cyclohexanes (see scheme). Significantly, there is no hint of the existence of sterically destabilizing 1,3‐diaxial nonbonding interactions in the axial conformers.